RESUMO
BACKGROUND: Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is associated with a dismal prognosis. Here, we report an analysis of CNS relapse for patients treated within the UK NCRI phase III R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) 14 versus 21 randomised trial. PATIENTS AND METHODS: The R-CHOP 14 versus 21 trial compared R-CHOP administered two- versus three weekly in previously untreated patients aged ≥18 years with bulky stage I-IV DLBCL (n = 1080). Details of CNS prophylaxis were retrospectively collected from participating sites. The incidence and risk factors for CNS relapse including application of the CNS-IPI were evaluated. RESULTS: 177/984 patients (18.0%) received prophylaxis (intrathecal (IT) methotrexate (MTX) n = 163, intravenous (IV) MTX n = 2, prophylaxis type unknown n = 11 and IT MTX and cytarabine n = 1). At a median follow-up of 6.5 years, 21 cases of CNS relapse (isolated n = 11, with systemic relapse n = 10) were observed, with a cumulative incidence of 1.9%. For patients selected to receive prophylaxis, the incidence was 2.8%. Relapses predominantly involved the brain parenchyma (81.0%) and isolated leptomeningeal involvement was rare (14.3%). Univariable analysis demonstrated the following risk factors for CNS relapse: performance status 2, elevated lactate dehydrogenase, IPI, >1 extranodal site of disease and presence of a 'high-risk' extranodal site. Due to the low number of events no factor remained significant in multivariate analysis. Application of the CNS-IPI revealed a high-risk group (4-6 risk factors) with a 2- and 5-year incidence of CNS relapse of 5.2% and 6.8%, respectively. CONCLUSION: Despite very limited use of IV MTX as prophylaxis, the incidence of CNS relapse following R-CHOP was very low (1.9%) confirming the reduced incidence in the rituximab era. The CNS-IPI identified patients at highest risk for CNS recurrence. CLINICALTRIALS.GOV: ISCRTN number 16017947 (R-CHOP14v21); EudraCT number 2004-002197-34.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Anticorpos Monoclonais Murinos/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prednisona/administração & dosagem , Estudos Prospectivos , Rituximab/administração & dosagem , Vincristina/administração & dosagemRESUMO
BACKGROUND: There is an on-going debate whether 2- or 3-weekly administration of R-CHOP is the preferred first-line treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL). The UK NCRI R-CHOP14v21 randomized phase 3 trial did not demonstrate a difference in outcomes between R-CHOP-14 and R-CHOP-21 in newly diagnosed DLBCL patients aged 19-88 years, but data on elderly patients have not been reported in detail so far. Here, we provide a subgroup analysis of patients ≥60 years treated on the R-CHOP14v21 trial with extended follow-up. PATIENTS AND METHODS: Six hundred and four R-CHOP14v21 patients ≥60 years were included in this subgroup analysis, with a median follow-up of 77.7 months. To assess the impact of MYC rearrangements (MYC-R) and double-hit-lymphoma (DHL) on outcome in elderly patients, we performed a joint analysis of cases with available molecular data from the R-CHOP14v21 (N = 217) and RICOVER-60 (N = 204) trials. RESULTS: Elderly DLBCL patients received high dose intensities with median total doses of ≥98% for all agents. Toxicities were similar in both arms with the exception of more grade ≥3 neutropenia (P < 0.0001) and fewer grade ≥3 thrombocytopenia (P = 0.05) in R-CHOP-21 versus R-CHOP-14. The elderly patient population had a favorable 5-year overall survival (OS) of 69% (95% CI: 65-73). We did not identify any subgroup of patients that showed differential response to either regimen. In multivariable analysis including individual factors of the IPI, gender, bulk, B2M and albumin levels, only age and B2M were of independent prognostic significance for OS. Molecular analyses demonstrated a significant impact of MYC-R (HR = 1.96; 95% CI: 1.22-3.16; P = 0.01) and DHL (HR = 2.21; 95% CI: 1.18-4.11; P = 0.01) on OS in the combined trial cohorts, independent of other prognostic factors. CONCLUSIONS: Our data support equivalence of both R-CHOP application forms in elderly DLBCL patients. Elderly MYC-R and DHL patients have inferior prognosis and should be considered for alternative treatment approaches. TRIAL NUMBERS: ISCRTN 16017947 (R-CHOP14v21); NCT00052936 (RICOVER-60).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/genética , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genética , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , Rearranjo Gênico , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Seleção de Pacientes , Medicina de Precisão , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Fatores de Risco , Rituximab , Fatores de Tempo , Resultado do Tratamento , Reino Unido , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
BACKGROUND: Lumbar microdiscectomy (LMD) is a commonly performed neurosurgical procedure. We set up a prospective, double blind, randomised, controlled trial to test the hypothesis that presenting the removed disc material to patients after LMD improves patient outcome. METHODS: Adult patients undergoing LMD for radiculopathy caused by a prolapsed intervertebral disc were randomised into one of two groups, termed experimental and control. Patients in the experimental group were given their removed disc fragments whereas patients in the control group were not. Patients were unaware of the trial hypothesis and investigators were blinded to patient group allocation. Outcome was assessed between 3 and 6 months after LMD. Primary outcome measures were the degree of improvement in sciatica and back pain reported by the patients. Secondary outcome measures were the degree of improvement in leg weakness, paraesthesia, numbness, walking distance and use of analgesia reported by the patients. RESULTS: Data from 38 patients in the experimental group and 36 patients in the control group were analysed. The two groups were matched for age, sex and preoperative symptoms. More patients in the experimental compared with the control group reported improvements in leg pain (91.5 vs 80.4%; p<0.05), back pain (86.1 vs 75.0%; p<0.05), limb weakness (90.5 vs 56.3%; p<0.02), paraesthesia (88 vs 61.9%; p<0.05) and reduced analgesic use (92.1 vs 69.4%; p<0.02) than preoperatively. CONCLUSION: Presentation of excised disc fragments is a cheap and effective way to improve outcome after LMD.
Assuntos
Discotomia/psicologia , Disco Intervertebral/patologia , Procedimentos Neurocirúrgicos/psicologia , Adulto , Dor nas Costas/terapia , Discotomia/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/psicologia , Procedimentos Neurocirúrgicos/efeitos adversos , Ciática/cirurgia , Resultado do Tratamento , CaminhadaRESUMO
The study was designed to compare clofarabine plus daunorubicin vs daunorubicin/ara-C in older patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS). Eight hundred and six untreated patients in the UK NCRI AML16 trial with AML/high-risk MDS (median age, 67 years; range 56-84) and normal serum creatinine were randomised to two courses of induction chemotherapy with either daunorubicin/ara-C (DA) or daunorubicin/clofarabine (DClo). Patients were also included in additional randomisations; ± one dose of gemtuzumab ozogamicin in course 1; 2v3 courses and ± azacitidine maintenance. The primary end point was overall survival. The overall response rate was 69% (complete remission (CR) 60%; CRi 9%), with no difference between DA (71%) and DClo (66%). There was no difference in 30-/60-day mortality or toxicity: significantly more supportive care was required in the DA arm even though platelet and neutrophil recovery was significantly slower with DClo. There were no differences in cumulative incidence of relapse (74% vs 68%; hazard ratio (HR) 0.93 (0.77-1.14), P=0.5); survival from relapse (7% vs 9%; HR 0.96 (0.77-1.19), P=0.7); relapse-free (31% vs 32%; HR 1.02 (0.83-1.24), P=0.9) or overall survival (23% vs 22%; HR 1.08 (0.93-1.26), P=0.3). Clofarabine 20 mg/m2 given for 5 days with daunorubicin is not superior to ara-C+daunorubicin as induction for older patients with AML/high-risk MDS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Nucleotídeos de Adenina/administração & dosagem , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Arabinonucleosídeos/administração & dosagem , Causas de Morte , Clofarabina , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Feminino , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Análise de Sobrevida , Resultado do TratamentoRESUMO
ADMIRE was a multicenter, randomized-controlled, open, phase IIB superiority trial in previously untreated chronic lymphocytic leukemia. Conventional front-line therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). Initial evidence from non-randomized phase II trials suggested that the addition of mitoxantrone to FCR (FCM-R) improved remission rates. Two hundred and fifteen patients were recruited to assess the primary end point of complete remission (CR) rates according to International Workshop on Chronic Lymphocytic Leukemia criteria. Secondary end points were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity and safety. At final analysis, CR rates were 69.8 FCR vs 69.3% FCM-R (adjusted odds ratio (OR): 0.97; 95% confidence interval (CI): (0.53-1.79), P=0.932). MRD-negativity rates were 59.3 FCR vs 50.5% FCM-R (adjusted OR: 0.70; 95% CI: (0.39-1.26), P=0.231). During treatment, 60.0% (n=129) of participants received granulocyte colony-stimulating factor as secondary prophylaxis for neutropenia, a lower proportion on FCR compared with FCM-R (56.1 vs 63.9%). The toxicity of both regimens was acceptable. There are no significant differences between the treatment groups for PFS and OS. The trial demonstrated that the addition of mitoxantrone to FCR did not increase the depth of response. Oral FCR was well tolerated and resulted in impressive responses in terms of CR rates and MRD negativity compared with historical series with intravenous chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Adulto , Idoso , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Neoplasia Residual , Neutropenia/tratamento farmacológico , Neutropenia/prevenção & controle , Indução de Remissão , Rituximab/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
We have studied a patient who presented with clinical features suggestive of chronic myeloid leukemia in accelerated phase. BCR-ABL transcripts were undetectable by reverse transcription-PCR, but a novel reciprocal translocation, t(5;10)(q33;q21.2), was seen by standard cytogenetic analysis. Chromosome band 5q33 contains the gene encoding the platelet-derived growth factor beta receptor (PDGFbetaR), the receptor tyrosine kinase that is disrupted by the t(5;7), t(5;12), and t(5;14) in myeloid disorders, resulting in the fusion of PDGFbetaR to HIP1, TEL/ETV6, and CEV14, respectively. Southern analysis with PDGFbetaR cDNA revealed novel bands in patient but not control DNA after digestion with several restriction enzymes, indicating that this gene is also targeted by the t(5;10). Fluorescence in situ hybridization analysis of chromosome 5 indicated that a small inversion at 5q33 had taken place in addition to the interchromosomal translocation. The site of the chromosome 10 breakpoint fell within YAC 940e4. Because all PDGFbetaR fusions described thus far result in splicing to a common exon of this gene, we performed 5'-rapid amplification of cDNA ends PCR on patient RNA. Several clones were isolated in which PDGFbetaR fused in frame to H4/D10S170, a previously described ubiquitously expressed gene that is fused to the ret protein tyrosine kinase to form the PTC-1 oncogene in approximately 20% of papillary thyroid carcinomas. The presence of H4-PDGFbetaR chimeric mRNA in the patient was confirmed by reverse transcription-PCR; reciprocal PDGFbeta1R-H4 transcripts were not detected. We conclude that t(5;10)(q33;q21.2) is a novel translocation in BCR-ABL-negative chronic myeloid leukemia and that this abnormality results in an H4-PDGFbetaR fusion gene. This finding further strengthens the association between myeloproliferative disorders and deregulated tyrosine kinases.
Assuntos
Cromossomos Humanos Par 10 , Cromossomos Humanos Par 5 , Proteínas de Drosophila , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Transtornos Mieloproliferativos/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Proteínas Recombinantes de Fusão/genética , Translocação Genética , Sequência de Aminoácidos , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Artificiais de Levedura , Proteínas de Fusão bcr-abl/análise , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-ret , Receptores Proteína Tirosina Quinases/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The t(14;18) translocation is found in the majority follicular lymphomas and some high grade B-cell lymphomas. This is results in deregulation of the BCL-2 gene and appears to play a role in oncogenesis. Various numbers of cells from a cell line derived spontaneously from a patient with B-cell lymphoma bearing the t(14;18) translocation and negative for the Epstein-Barr virus (EBV) were injected by IP, IV, and SC routes into SCID mice. The mice developed lymphoma bearing the t(14;18) translocation with as few as 5 x 10(6) cells within 28 days. This was determined by histological examination. The higher the cell inoculation the more rapidly the lymphoma developed. Engraftment of the tumour cells was determined by PCR for the t(14;18) breakpoint region on peripheral blood samples and could be detected prior to development of overt lymphoma. Having established a lymphoma model the cells were treated with antisense oligonucleotides to the first open reading frame of the BCL-2 gene prior to inoculation of the SCID mice. Control treatments with sense and nonsense oligonucleotides was also performed. At 28 days the sense, nonsense and untreated cell SCID mice had developed lymphoma, however, the antisense treated group failed to develop lymphoma. The findings demonstrate the modelling of B-cell lymphoma bearing the t(14;18) translocation and the ability to modify the lymphoma process with the use of antisense oligonucleotides to the BCL-2 gene. Reduction of the BCL2 protein suppresses the oncogenic potential of these lymphoma cells confirming that it plays an essential role in the development of malignancy.
Assuntos
Linfoma de Células B/genética , Oligonucleotídeos Antissenso/farmacologia , Proteínas Proto-Oncogênicas/genética , Animais , Sequência de Bases , Divisão Celular/genética , Linhagem Celular , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 18 , Modelos Animais de Doenças , Humanos , Linfoma de Células B/patologia , Camundongos , Camundongos SCID , Dados de Sequência Molecular , Oligonucleotídeos Antissenso/genética , Proteínas Proto-Oncogênicas c-bcl-2 , Translocação Genética , Células Tumorais CultivadasRESUMO
Transformation of CLL into a large cell lymphoma has an incidence of 3-5%. We have studied 101 cases of CLL treated with fludarabine over a 10-year period (1990-2000) and observed a 12% incidence of transformation. In six of 12 patients, transformation was documented within 4 months following treatment with fludarabine. Pathological material, available in nine cases, was investigated for latent EBV by staining for LMP-1 by immunohistochemistry and EBERs-1 and 2 by in situ hybridisation. LMP-1 and EBERs were demonstrated in three of the nine samples. In two cases there was a different pattern of immunoglobulin gene rearrangement in the transformed cells assessed by PCR (FR3 fragment) compared to the original CLL clone. One of these two cases showed evidence of latent EBV. The other seven cases, of which two were EBV positive, showed identical pattern of Ig gene rearrangement in both the CLL and the transformed cells. We suggest that the relatively high incidence of transformation in this series may be due to immunosuppression mainly related to fludarabine, although other agents and prior therapies may have also contributed.
Assuntos
Antineoplásicos/uso terapêutico , Herpesvirus Humano 4/isolamento & purificação , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/virologia , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transformação Celular Neoplásica , Progressão da Doença , Feminino , Humanos , Rim/patologia , Leucemia Linfocítica Crônica de Células B/patologia , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Células de Reed-Sternberg/parasitologia , Resultado do Tratamento , Proteína Supressora de Tumor p53/genéticaRESUMO
Immune haemolytic anaemia (IHA) is a recognised complication after allogeneic stem cell transplantation (SCT) and occurs more frequently if marrow cells have been subjected to T cell depletion (TCD). Among 58 consecutive patients who underwent TCD-allogeneic SCT from volunteer unrelated donors for the treatment of CML at the Hammersmith Hospital during a 3-year period (1 March 1996 to 28 February 1999) we identified nine cases of IHA. All patients had a strongly positive direct and indirect antiglobulin test and in eight patients the serological findings were typical of warm-type haemolysis often with antibody specificities within the Rh system. All nine cases had clinically significant haemolysis and were treated initially with prednisolone and immunoglobulin. The onset of IHA coincided with the occurrence of leukaemic relapse in six cases, and the presence of host haemopoiesis confirmed by lineage-specific chimerism in all four cases studied. Five patients received donor lymphocyte infusions (DLI); in three molecular remission and the restoration of full donor chimerism coincided with resolution of haemolysis. We conclude that in the context of leukaemic relapse, DLI is an effective therapy for IHA following allografts involving TCD.
Assuntos
Anemia Hemolítica Autoimune/etiologia , Transplante de Medula Óssea/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Depleção Linfocítica/efeitos adversos , Adolescente , Adulto , Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/terapia , Transplante de Medula Óssea/imunologia , Transplante de Medula Óssea/métodos , Feminino , Humanos , Isoanticorpos/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Transfusão de Linfócitos , Masculino , Recidiva , Estudos Retrospectivos , Quimeras de Transplante , Transplante Homólogo/efeitos adversos , Transplante Homólogo/imunologia , Transplante Homólogo/métodos , Resultado do TratamentoRESUMO
INTRODUCTION: Allogeneic stem cell transplantation is a potentially curative option for patients with CML. The optimal donor is an HLA-identical sibling but transplants using unrelated volunteers can also be successful. The factors influencing survival after allogeneic SCT for CML are reasonably well defined. Recently however, the Seattle group have emphasised the influence of a high marrow cell dose on outcome following volunteer unrelated donor SCT for high risk acute leukaemia. MATERIALS AND METHODS: We have sought to define factors impacting on transplant related mortality (TRM) in a population of CML patients after allografting with matched sibling or alternative stem cell donors at a single centre over a 20-year period, with emphasis on infused marrow cell dose. Factors entered into a multivariate analysis were: recipient age, recipient CMV serostatus, disease phase, donor sex, cell dose and frequency of CTLP reactivity. RESULTS: In multivariate analysis four factors had an adverse effect on TRM when using a VUD: low marrow cell dose (<3.65 x 10(8) TNC/kg, relative risk 2.05, CI 1.08-3.90, P = 0.029), late disease phase (relative risk 1.68, CI 1.03-2.74, P = 0.038), patient CMV seropositivity (relative risk 1.98, CI 1.25-3.13, P = 0.004) and high frequency of CTLP (relative risk 1.93, CI 1.18-3.13, P = 0.008). For HLA-identical sibling donor transplants the only factor that adversely impacted on TRM was late disease phase (P = 0.0004 in univariate analysis). CONCLUSION: High infused cell dose is a new modifiable factor associated with reduced TRM following allogeneic SCT using an unrelated donor for the treatment of CML. The data support the recommendation that bone marrow harvest teams should aim to collect the highest possible number of nucleated cells for recipients of unrelated donor transplants.
Assuntos
Transplante de Medula Óssea/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adulto , Células da Medula Óssea , Transplante de Medula Óssea/imunologia , Transplante de Medula Óssea/mortalidade , Contagem de Células , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Análise Multivariada , Prognóstico , Doadores de Tecidos , Transplante Homólogo/imunologia , Transplante Homólogo/métodos , Transplante Homólogo/mortalidade , Resultado do TratamentoRESUMO
Significant aortic stenosis is prevalent amongst elderly people. It may be subclinical, manifesting only as a murmur, but can still cause unexpected death with little warning after symptoms develop. Recent studies have highlighted the unreliability of the classical clinical signs of severe aortic stenosis, leading to concern that some patients may not be referred appropriately for echocardiography. Here, we review the evidence for the accuracy of each sign. We suggest that the assessment of the patient with a systolic murmur should be reappraised, and offer guidelines toward improving the recognition of aortic stenosis in the community.
Assuntos
Estenose da Valva Aórtica/diagnóstico , Sopros Cardíacos/etiologia , Idoso , Estenose da Valva Aórtica/complicações , Diagnóstico Diferencial , Humanos , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
We present a short report here of two more patients with trisomy 2 as the sole chromosomal abnormality in a hematologic malignancy. Although trisomy 2 is a recognized abnormality in neoplasms, particularly hepatoblastomas, to the best of our knowledge only three other cases have been reported with trisomy 2, in patients with a hematologic malignancy. The two cases presented here of myelodysplastic syndrome transforming to acute myeloblastic leukemia and chronic myelomonocytic leukemia showed trisomy 2 as the sole abnormality.
Assuntos
Cromossomos Humanos Par 2 , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicas/genética , Trissomia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , MosaicismoRESUMO
Chromosome rearrangements of chromosome 11 at band 1 1q23 are detected in a high proportion of infant leukemias (
RESUMO
The efficacy of piperacillin/tazobactam (PIPC/TBT) in combination with gentamicin was assessed as empirical therapy in 44 febrile neutropenic patients with haematological malignancy. A favourable response to therapy was seen in 67% patients overall and in 57% of patients with microbiologically documented infection. PIPC/TBT demonstrated good clinical and in vitro activity against isolated pathogens, particularly Gram positive cocci such as Staphylococcus epidermidis. The MIC of both Gram positive and Gram negative pathogens to PIPC was reduced in the presence of TBT. PIPC/TBT plus gentamicin is a safe and effective combination for empirical therapy in febrile neutropenic patients, even in a unit with a predominance of Gram positive infections.
Assuntos
Infecções Bacterianas/tratamento farmacológico , Quimioterapia Combinada/uso terapêutico , Febre/tratamento farmacológico , Leucemia/complicações , Linfoma/complicações , Neutropenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Antineoplásicos/efeitos adversos , Transplante de Medula Óssea/efeitos adversos , Feminino , Febre/etiologia , Gentamicinas/uso terapêutico , Humanos , Leucemia/tratamento farmacológico , Leucemia/cirurgia , Linfoma/tratamento farmacológico , Linfoma/cirurgia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Neutropenia/etiologia , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Tazobactam , Inibidores de beta-LactamasesAssuntos
Transplante de Medula Óssea/fisiologia , Hemostasia , Biomarcadores , Fatores de Coagulação Sanguínea/análise , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/métodos , Bussulfano/uso terapêutico , Ciclofosfamida/uso terapêutico , Endotélio Vascular/patologia , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Valor Preditivo dos Testes , Transplante Autólogo , Transplante Homólogo , Irradiação Corporal TotalRESUMO
Rupture of the quadriceps tendon is an uncommon injury and rapid diagnosis is important because delay in surgical repair generally is believed to adversely affect outcome. One study of 20 patients suggests repair should be done during the first 48 to 72 hours postinjury to achieve a successful outcome and late repair led to unsatisfactory recovery. Cases of delayed tendon repair have been reported, the longest to our knowledge being 11 months before surgical intervention. We present a case of successful outcome of a quadriceps tendon rupture reconstructed at least 8 years after occurrence and a review of the literature of delayed reconstructions. We show that successful restoration of extensor mechanism function can be achieved several years after tendon rupture.
Assuntos
Traumatismos do Joelho/cirurgia , Procedimentos de Cirurgia Plástica , Traumatismos dos Tendões/cirurgia , Tendões/cirurgia , Idoso de 80 Anos ou mais , Feminino , Humanos , Traumatismos do Joelho/complicações , Traumatismos do Joelho/patologia , Articulação do Joelho , Ruptura/cirurgia , Traumatismos dos Tendões/complicações , Traumatismos dos Tendões/patologia , Tendões/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Microangiopathic haemolytic anaemia (MAHA) is a well recognized complication of disseminated carcinoma and its treatment. It is however, rarely seen with localized carcinoma. The case presented here is a previously unreported association of a patient, who having been successfully treated for MAHA, was found to have occult breast carcinoma on a routine screening mammogram six months after the haemolytic episode.
Assuntos
Adenocarcinoma/complicações , Anemia Hemolítica/complicações , Neoplasias da Mama/complicações , Neoplasias Primárias Desconhecidas/complicações , Adenocarcinoma/sangue , Adenocarcinoma/diagnóstico por imagem , Anemia Hemolítica/tratamento farmacológico , Anemia Hemolítica/terapia , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico por imagem , Dexametasona/uso terapêutico , Epoprostenol/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/sangue , Troca Plasmática , Pneumonia/complicações , Radiografia , Vincristina/uso terapêuticoRESUMO
Acute leukaemia of infancy is associated with abnormalities at chromosome band 11q23, and has a poor prognosis. The gene involved. Mixed Lineage Leukaemia (MLL), has been identified and has the characteristics of a transcription factor. The BCL-2 gene responsible for blocking of programmed cell death is highly expressed in a number of haematological malignancies, both with and without the t(14;18) translocation. Those without the translocation include acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML) and chronic lymphocytic leukaemia (CLL). In these diseases the BCL-2 protein is implicated in drug resistance to apoptosis-inducing chemotherapeutic agents. High BCL-2 expression is also associated with autonomous growth of leukaemic blasts in culture and predicts a poor prognosis. The SEM cell line, established using blood lymphoblasts from a 5-year-old girl in first relapse with t(4;11) ALL, expresses lymphoid (CD19) and myeloid (CD13) cell surface markers. In cell culture, a subpopulation of cells (< 30%) express the BCL-2 protein. A reproducible model of true biphenotypic leukaemia in the SCID mouse has been established using the SEM-K2 cell line (a subclone of the SEM cell line). Between 5 and 50 million cells injected intravenously (i.v.) produce complete replacement of the murine bone marrow by day 30, associated with blood lymphoblastosis and infiltration of the spleen. No tumour masses were seen. Fluorescence in situ hybridization (FISH) analysis of the cell line and blood from the SCID-human (SCID-hu) chimaera has confirmed the presence of the t(4;11). Reverse transcriptional-polymerase chain reaction (RT-PCR) reveals that the breakpoint lies between exons 7 and 8 of the MLL-1 gene on chromosome 11 (the main breakpoint region). A further translocation, t(7;13), has been identified. Fluorescent antibody cell sorter (FACS) analysis of tumour material recovered from the SCID-hu model confirms expression of CD19 and CD13 identical to that of the cell line. In addition, BCL-2 expression in SCID-hu marrow is now seen in the majority of tumour cells. BCL-2 expression appears to confer a survival advantage to the blast cells in vivo. This reproducible model of biphenotypic leukaemia suggests that BCL-2 expression may play a role in leukaemogenesis. The model is suitable for the investigation of gene-targeted therapy, including antisense oligonucleotides, directed towards the MLL and BCL-2 genes.
Assuntos
Cromossomos Humanos Par 11 , Cromossomos Humanos Par 4 , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Proto-Oncogênicas/genética , Animais , Sequência de Bases , Medula Óssea/patologia , Modelos Animais de Doenças , Feminino , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Masculino , Camundongos , Camundongos SCID , Dados de Sequência Molecular , Transplante de Neoplasias , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Proteínas Proto-Oncogênicas c-bcl-2 , Quimeras de Transplante , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
Defects in stromal cell function have been demonstrated in a number of aplastic anaemia (AA) patients. Here we have studied a patient with severe AA and abnormal stromal cell function who underwent bone marrow transplantation (BMT). The objective of this study was to investigate the timing and the mechanism of correction of the stromal defect after transplantation. The patient, a 25-year-old woman with severe AA, underwent BMT from her brother. BM was obtained from the patient on five occasions: 2 weeks pre BMT, and 3, 8, 16 and 21 months post BMT. Stromal cells were grown to confluence and recharged with purified CD34+ cells from normal donors. The support of such cells, as assessed by weekly colony-forming assay (CFU) of non-adherent cells, was compared with that of stromal layers grown from normal BM. A novel technique of combined fluorescence in situ hybridization (FISH) and immunocytochemistry was used to determine the origin of specific stromal cell types on cytospins of stroma post BMT. Stromal function was defective at 2 weeks pre BMT and at 3 months post BMT, but returned to normal at 8 and 16 months post BMT. At 21 months post BMT, stromal fibroblasts and endothelial cells were shown to be of recipient origin, and macrophages and T cells were of donor origin. We present here evidence in a case of severe AA for defective stromal function before BMT and delayed normalization of function after BMT. This correlated with engraftment of donor macrophages and T cells, but not fibroblasts and endothelial cells.